scholarly journals Casein kinase 1 gamma integrates oxidative stress and innate immune responses

2021 ◽  
Author(s):  
Long Ma ◽  
Yiman Hu ◽  
Zhaofa Xu
Keyword(s):  
Oxidative Stress ◽  
Innate Immunity ◽  
Molecular Mechanisms ◽  
Casein Kinase ◽  
Innate Immune Responses ◽  
Casein Kinase 1 ◽  
C Elegans ◽  
Animal Survival ◽  
Immunity Genes ◽  
Excess Iodide

Abstract Animals utilize associated pathways to elicit responses to oxidative stress and infection. The molecular mechanisms coordinating these pathways remain unclear. Here, using C. elegans we identified the highly conserved casein kinase 1 gamma CSNK-1 (also known as CK1g or CSNK1G), as a key regulator of these processes. csnk-1 interacted with the bli-3/tsp-15/doxa-1 dual oxidase genes by nonallelic noncomplementation to negatively regulate animal survival in excess iodide, an oxidative stressor. A conserved interaction was detected between DOXA-1 and CSNK-1 and between their human homologs DUOXA2 and CSNK1G2. csnk-1 deficiency resulted in upregulated expression of innate immunity genes and increased animal survival in the pathogenic Pseudomonas aeruginosa PA14. Phosphoproteomic analyses identified decreased phosphorylation of key innate immunity regulators NSY-1 MAPKKK and LIN-45 Raf in csnk-1(lf) mutants. Indeed, NSY-1 and LIN-45 pathways were required for the increased survival of csnk-1-deficient animals in PA14. Further analyses suggest that CSNK-1 and SKN-1 Nrf2 might act in parallel to regulate oxidative stress response. Together, we propose that CSNK-1 CSNK1G plays a novel pivotal role in integrating animal’s responses to oxidative stress and pathogens.

scholarly journals The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

2021 ◽  
Author(s):  
Phillip Wibisono ◽  
Shawndra Wibisono ◽  
Jan Watteyne ◽  
Chia-Hui Chen ◽  
Durai Sellegounder ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Genes ◽  
C Elegans ◽  
Adaptive Immune ◽  
Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

scholarly journals PKA/KIN-1 mediates innate immune responses to bacterial pathogens in Caenorhabditis elegans

2017 ◽  
Vol 23 (8) ◽  
pp. 656-666 ◽  
Author(s):  
Yi Xiao ◽  
Fang Liu ◽  
Pei-ji Zhao ◽  
Cheng-Gang Zou ◽  
Ke-Qin Zhang
Keyword(s):  
Innate Immunity ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Immune Responses ◽  
Innate Immune ◽  
Autophagic Flux ◽  
Innate Immune Responses ◽  
C Elegans ◽  
Downstream Effector ◽  
Model Animal

The genetically tractable organism Caenorhabditis elegans is a powerful model animal for the study of host innate immunity. Although the intestine and the epidermis of C. elegans that is in contact with pathogens are likely to function as sites for the immune function, recent studies indicate that the nervous system could control innate immunity in C. elegans. In this report, we demonstrated that protein kinase A (PKA)/KIN-1 in the neurons contributes to resistance against Salmonella enterica infection in C. elegans. Microarray analysis revealed that PKA/KIN-1 regulates the expression of a set of antimicrobial effectors in the non-neuron tissues, which are required for innate immune responses to S. enterica. Furthermore, PKA/KIN-1 regulated the expression of lysosomal genes during S. enterica infection. Our results suggest that the lysosomal signaling molecules are involved in autophagy by controlling autophagic flux, rather than formation of autophagosomes. As autophagy is crucial for host defense against S. enterica infection in a metazoan, the lysosomal pathway also acts as a downstream effector of the PKA/KIN-1 signaling for innate immunity. Our data indicate that the PKA pathway contributes to innate immunity in C. elegans by signaling from the nervous system to periphery tissues to protect the host against pathogens.

scholarly journals Specificity and Complexity of the Caenorhabditis elegans Innate Immune Response

2007 ◽  
Vol 27 (15) ◽  
pp. 5544-5553 ◽  
Author(s):  
Scott Alper ◽  
Sandra J. McBride ◽  
Brad Lackford ◽  
Jonathan H. Freedman ◽  
David A. Schwartz
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Signaling Pathways ◽  
Large Set ◽  
Immune Signaling ◽  
C Elegans ◽  
Immunity Genes ◽  
Simple Model System ◽  
Overlapping Sets

ABSTRACT In response to infection, Caenorhabditis elegans produces an array of antimicrobial proteins. To understand the C. elegans immune response, we have investigated the regulation of a large, representative sample of candidate antimicrobial genes. We found that all these putative antimicrobial genes are expressed in tissues exposed to the environment, a position from which they can ward off infection. Using RNA interference to inhibit the function of immune signaling pathways in C. elegans, we found that different immune response pathways regulate expression of distinct but overlapping sets of antimicrobial genes. We also show that different bacterial pathogens regulate distinct but overlapping sets of antimicrobial genes. The patterns of genes induced by pathogens do not coincide with any single immune signaling pathway. Thus, even in this simple model system for innate immunity, striking specificity and complexity exist in the immune response. The unique patterns of antimicrobial gene expression observed when C. elegans is exposed to different pathogens or when different immune signaling pathways are perturbed suggest that a large set of yet to be identified pathogen recognition receptors (PRRs) exist in the nematode. These PRRs must interact in a complicated fashion to induce a unique set of antimicrobial genes. We also propose the existence of an “antimicrobial fingerprint,” which will aid in assigning newly identified C. elegans innate immunity genes to known immune signaling pathways.

scholarly journals Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Elizabeth Moreno-Arriola ◽  
Noemí Cárdenas-Rodríguez ◽  
Elvia Coballase-Urrutia ◽  
José Pedraza-Chaverri ◽  
Liliana Carmona-Aparicio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Second Messengers ◽  
Model Organism ◽  
Human Diseases ◽  
C Elegans ◽  
Molecular Bases

Caenorhabditis elegansis a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic levelin vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes.C. elegansdisplays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance ofC. elegansas an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology.

scholarly journals Exploring Target Genes Involved in the Effect of Quercetin on the Response to Oxidative Stress in Caenorhabditis elegans

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 585 ◽  
Author(s):  
Begoña Ayuda-Durán ◽  
Susana González-Manzano ◽  
Antonio Miranda-Vizuete ◽  
Eva Sánchez-Hernández ◽  
Marta R. Romero ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Fluorescent Protein ◽  
Biological Activities ◽  
Biological Effects ◽  
Knockout Mutant ◽  
C Elegans

Quercetin is one the most abundant flavonoids in the human diet. Although it is well known that quercetin exhibits a range of biological activities, the mechanisms behind these activities remain unresolved. The aim of this work is to progress in the knowledge of the molecular mechanisms involved in the biological effects of quercetin using Caenorhabditis elegans as a model organism. With this aim, the nematode has been used to explore the ability of this flavonoid to modulate the insulin/insulin-like growth factor 1(IGF-1) signaling pathway (IIS) and the expression of some genes related to stress response. Different methodological approaches have been used, i.e., assays in knockout mutant worms, gene expression assessment by RT-qPCR, and C. elegans transgenic strains expressing green fluorescent protein (GFP) reporters. The results showed that the improvement of the oxidative stress resistance of C. elegans induced by quercetin could be explained, at least in part, by the modulation of the insulin signaling pathway, involving genes age-1, akt-1, akt-2, daf-18, sgk-1, daf-2, and skn-1. However, this effect could be independent of the transcription factors DAF-16 and HSF-1 that regulate this pathway. Moreover, quercetin was also able to increase expression of hsp-16.2 in aged worms. This observation could be of particular interest to explain the effects of enhanced lifespan and greater resistance to stress induced by quercetin in C. elegans, since the expression of many heat shock proteins diminishes in aging worms.

scholarly journals Triggering of Suicidal Erythrocyte Death by Bexarotene

2016 ◽  
Vol 40 (5) ◽  
pp. 1239-1251 ◽  
Author(s):  
Abdulla Al Mamun Bhuyan ◽  
Rosi Bissinger ◽  
Hang Cao ◽  
Florian Lang
Keyword(s):  
Oxidative Stress ◽  
Cell Membrane ◽  
Statistical Significance ◽  
Annexin V ◽  
Hemoglobin Concentration ◽  
Casein Kinase ◽  
Forward Scatter ◽  
Casein Kinase 1 ◽  
Suicidal Death ◽  
Phosphatidylserine Translocation

Background/Aims: The retinoid X receptor agonist bexarotene is utilized for the treatment of cutaneous T-cell lymphoma and is effective in several further malignancies. The substance counteracts tumor growth in part by triggering suicidal death or apoptosis of tumor cells. Side effects of bexarotene treatment include anemia. Theoretically, bexarotene induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling potentially stimulating eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), induction of oxidative stress, increase of ceramide abundance, as well as activation of staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, D4476 sensitive casein kinase 1, and zVAD sensitive caspases. The present study explored, whether bexarotene induces eryptosis and, if so, whether its effect involves Ca2+ entry, oxidative stress, ceramide, kinases and/or caspases. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was estimated from hemoglobin concentration in the supernatant. Results: A 48 hours exposure of human erythrocytes to bexarotene (≥ 0.4 µg/ml) significantly increased the percentage of annexin-V-binding cells without significantly modifying forward scatter. Bexarotene significantly increased Fluo3-fluorescence and DCFDA fluorescence. Bexarotene tended to increase ceramide abundance, an effect, however, not reaching statistical significance. The effect of bexarotene on annexin-V-binding was significantly blunted by removal of extracellular Ca2+ and by addition of D4476 (10 µM), but not by addition of staurosporine (1 µM), SB203580 (2 µM), or zVAD (10 µM). Conclusions: Bexarotene triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca2+ entry, oxidative stress, and activation of D4476 sensitive casein kinase.

scholarly journals Casein Kinase 1 Is a Novel Negative Regulator of E-Cadherin-Based Cell-Cell Contacts

2007 ◽  
Vol 27 (10) ◽  
pp. 3804-3816 ◽  
Author(s):  
Sophie Dupre-Crochet ◽  
Angélica Figueroa ◽  
Catherine Hogan ◽  
Emma C. Ferber ◽  
Carl Uli Bialucha ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Phosphorylation Site ◽  
Specific Inhibitor ◽  
Casein Kinase ◽  
Negative Regulator ◽  
Casein Kinase 1 ◽  
Cell Contacts ◽  
E Cadherin ◽  
Cell Cell

ABSTRACT Cadherins are the most crucial membrane proteins for the formation of tight and compact cell-cell contacts. Cadherin-based cell-cell adhesions are dynamically established and/or disrupted during various physiological and pathological processes. However, the molecular mechanisms that regulate cell-cell contacts are not fully understood. In this paper, we report a novel functional role of casein kinase 1 (CK1) in the regulation of cell-cell contacts. Firstly, we observed that IC261, a specific inhibitor of CK1, stabilizes cadherin-based cell-cell contacts, whereas the overexpression of CK1 disrupts them. CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846, a highly conserved residue between classical cadherins. Constitutively phosphorylated E-cadherin (S846D) is unable to localize at cell-cell contacts and has decreased adhesive activity. Furthermore, phosphorylated E-cadherin (S846D) has weaker interactions with β-catenin and is internalized more efficiently than wild-type E-cadherin. These data indicate that CK1 is a novel negative regulator of cadherin-based cell-cell contacts.

scholarly journals A quantitative genome-wide RNAi screen in C. elegans for antifungal innate immunity genes

BMC Biology ◽  
2016 ◽  
Vol 14 (1) ◽  
Author(s):  
Olivier Zugasti ◽  
Nishant Thakur ◽  
Jérôme Belougne ◽  
Barbara Squiban ◽  
C. Léopold Kurz ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Rnai Screen ◽  
C Elegans ◽  
Genome Wide ◽  
Immunity Genes

scholarly journals Genes misregulated in C. elegans deficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes

RNA ◽  
2007 ◽  
Vol 13 (7) ◽  
pp. 1090-1102 ◽  
Author(s):  
N. C. Welker ◽  
J. W. Habig ◽  
B. L. Bass
Keyword(s):  
Innate Immunity ◽  
C Elegans ◽  
Immunity Genes

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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